The development of the nervous system of neurological mutant mice is being studied by morphological methods, organotypic culture experiments, and behavioral and pharmacological observations. Mutants deficient in CNS myelin, quaking, jimpy, and myelin synthesis defect (MSD), are studied by light and electron microscopy to quantitate and characterize the myelin deficiency. Using marker genes, affected animals are identified at birth and their brain tissue placed in organotypic culture to determine the effect of the culture system on the expression of the disease. Jimpy and MSD, both sex linked recessive lethals, are more similar morphologically than would have been expected from previously published studies, and may be identical. The latter idea is being tested by appropriate breeding programs. In culture, both jimpy and MSD express the disease on the coverslip. Myelin is drastically reduced in amount, it is distributed in clusters as it is in the whole animal, and most of these clusters are visible in the living culture. Quaking, an autosomal recessive with a milder myelin deficiency, different pathology, and longer survival, behaves enigmatically in culture. More myelin is formed by quaking cultures than by jimpy and MSD cultures, but almost none of it is visible in living quaking cultures. Ultrastructural studies now in progress are likely to assist in resolving this paradox. In a separate project, shaker-1 mutants, which ave absent inner ear function, circling behavior, and other hyperactive and abnormal behavior not explained by the inner ear disease, are under study. The circling of individual mice shows a constant directional preference and can be specifically influenced by drugs which are dopamine agonists or antagonists. This behavior and drug effect is being quantitated, its ontogeny investigated, and similar study extended to other circling mutants with different inner ear pathology but similar abnormal behavior.